The research proposed in the following grant application is aimed at establishing novel spectroscopic techniques to probe solution structures of molecules of biological interest. The spectroscopic method to be exploited is Vibrational Optical Activity (VOA), a relatively recently discovered technique of spectroscopy, which combines principles of vibrational spectroscopy and optical activity. Instrumentation for the observation of both experimental approaches to VOA, infrared Vibrational Circular Dichroism (VCD) and Raman Optical Activity (ROA), has been constructed in the applicant's laboratory during the last grant period. Unexpected difficulties with the ROA instrumentation have been overcome and ROA data are now available routinely. The spectroscopic efforts have centered, and will continue to center, around small molecules which model molecules of biological interest, and other systems designed such that the origin of VOA may be understood in terms of a detailed vibrational analysis. Consequently, efforts to synthesize and resolve small chiral species will be expanded. VOA data on these molecules will be obtained and interpreted in terms of model calculations, which are presently underway. Models of biological molecules, such as peptide fragments and small nucleotide polymers, will be synthesized such that conformational sensitivity of VOA may be established. In order to determine the identity of certain vibrations, the syntheses may involve the incorporation of specific probes the vibrations of which may be observed easily. Thus, the proposed research represents an integrated approach, involving instrument development, spectroscopic, synthetic and theoretical efforts, to augment presently available techniques to deduce solution conformation of biomolecules.